382 research outputs found

    Detailed study of perforated beams with closely spaced novel web opening.

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    This paper presents a detailed study of the behaviour of perforated steel beams with closely spaced web openings. Seven specimens including two typical cellular beams (i.e. circular web openings) and five perforated beams with novel web opening shapes were tested previously by the authors, to investigate the failure mode and load strength of the web-post between two adjacent web openings. These new novel web opening shapes improve the structural performance of the perforated beams with respect to web-post buckling failure. In addition, the manufacturing procedure of these novel web openings is improved and leads to sustainable design. The effects of web opening spacing/web opening depth of web-posts as well as the web opening depth/web thickness were studied to investigate the stability (slenderness) of the web-post subjected to vertical shear load. In comparison with the conventional cellular beams, significant advantages were obtained

    TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

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    Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response
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